Compositions of herbal formulations and uses thereof

ABSTRACT

Disclosed herein are herbal formulations for relief from symptoms of skin disease. The formulations can also be combined with an active or inactive pharmaceutical ingredient, and/or a pharmaceutically acceptable excipient.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.61/486,724, filed May 16, 2011, which is incorporated herein byreference in its entirety, including the drawings.

FIELD OF THE INVENTION

The present invention is in the field of formulations, and in particularherbal formulations, for the management of symptoms of skin conditions.

BACKGROUND OF THE DISCLOSURE

Human bodies have evolved over millions of years in harmony with nature.Certain natural products induce the human body to function moreefficiently at combating disease and adverse conditions. These productshelp the human body heal itself. Skin conditions, the most visible ofhuman maladies, have historically received the most attention when itcomes to the application of herbal remedies. Herbs have been used in thehealing of adverse skin conditions for thousands of years. Aloe vera,for example, is an herbal extract that has been used throughout historyas a skin soothant and healant. Even today, lotions containing aloe veraare used to help skin to heal after sunburn.

Despite advances in science, skin conditions remain prevalent and thealleviation of symptoms remains elusive. Humans must return to naturefrom whence they came to find suitable relief for these conditions.

SUMMARY OF THE INVENTION

Disclosed herein are compositions comprising a mixture of plant extractsobtained from at least two plants selected from the group consisting of:Achillea millefolium; Aesuculus hippocastanum; Althaea officinalis;Avena sativa; Berberis vulgaris; Capsella Bursa Pastoris; Cochleariaofficinalis; Conium maculatium; Ervum lens; Hamamelis virginiana;Hydrastis canadensis; Matricaria chamomilla; Nasturtium officinale;Phytolacca decendra; Pimpinella saxifraga; Populas alba; Populustremuloides; Rhus toxicodendron; Sambucus nigra; Sanguinaria Canadensis;Scrophularia nodosa; Smilax medica; Tussilago farfara; Veronicaofficinalis; and Vincetoxicum officinale. Also disclosed arecompositions comprising the above compositions and a pharmaceuticallyacceptable carrier, diluents, or excipient. In addition, disclosedherein are methods of treating skin conditions by using the abovecompositions.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the results of the application of the HAT-01formulation to psoriasis patients.

FIG. 2 is an illustration of the pilot trial study design conducted toevaluate the safety, benefit & tolerability of HAT-01 in patients withatopic dermatitis

FIG. 3 demonstrates the benefit of HAT-01 in a study of patients withatopic dermatitis.

FIG. 4 illustrates the benefit of HAT-01 in a study in patients withatopic dermatitis.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Disclosed herein are herbal compositions, based on a proprietarypreparation of traditional commonly used herbs. Our studies havedemonstrated that these formulations are potent and safe agents withbenefit in aiding the body to alleviate the symptoms of chronic skinconditions as described herein.

Thus, in the first aspect, disclosed herein are complex herbalpreparations containing a unique mixture of traditional commonly usedmultiple herbs. In some embodiments, the mixture comprises four herbalextract components. In certain embodiments, the disclosed preparationscomprise plant extracts.

The term “plant extract” or “plant extracts” as used herein refers to acomposition of extracted plant substances, including but not limited to:juices; macerations; concentrates; syrups; cold, heated, fluid and/orfermented extracts; powders; tablets; tinctures; herbal teas in the formof infusions or decoctions; poultices; lotions; creams; gels; ointments;salves; liniments; balms; oils; essential oils; suspensions; emulsions;compresses; dressings; fomentations; eyebaths; gargles; enemas; boluses;and other forms of extracted plant substances such as are known to thoseof ordinary skill in the arts of pharmacognosy, herbalism, and medicinalformulation. As used herein the term “plant extract” or “plant extracts”further contemplates the use of a solvent known to practitioners in thisart for the purpose of extraction and or formulation, including but notlimited to the use of one or more solvents such as water, an alcohol, apolyhydric alcohol, an ether, an ester, a carboxylic acid, an amide, acarbonate, supercritical fluid carbon dioxide, an ionic liquid, analkane, a petroleum-derived oil, a plant oil, or another solvent,wherein the solvent employed is optionally part of a pH-adjusted medium.The term “plant extract” or “plant extracts” as used herein furthercontemplates that the extract may have been obtained by the use of oneor more methods such as expression, absorption by steeping or otherwise,maceration, distillation, evaporation optionally with vacuumenhancement, freeze drying, and other methods known in the arts ofsubstance isolation from natural sources.

In some embodiments, the disclosed preparations comprise a mixture ofplant extracts from at least two plants selected from the groupconsisting of: Achillea millefolium (Yarrow); Aesuculus hippocastanum(Horsechestnut); Althaea officinalis (Althea mallow, or Marsh Mallow);Avena sativa (Oat); Berberis vulgaris (Barberry shrub); Capsella BursaPastoris (Shepherd's Purse); Cochlearia officinalis (Spoon Wort); Coniummaculatium (Hemlock); Ervum lens (Lentil); Hamamelis virginiana(Virginium Hamamelis); Hydrastis canadensis (Orange Root); Matricariachamomilla (Chamomil); Nasturtium officinale (Watercress); Phytolaccadecendra (Poke Root); Pimpinella saxifraga (Pimpernal); Populas alba(White poplar); Populus tremuloides (Trembling poplar; Quaking Aspen,Trembling Aspen, Quakies); Rhus toxicodendron (Ivy); Sambucus nigra(Elderberry); Sanguinaria Canadensis (Canadian Blood root); Scrophularianodosa (Figwort); Smilax medica (Sarasaparrilla); Tussilago farfara(Coltsfoot); Veronica officinalis (Speedwell); and Vincetoxicumofficinale (Swallow Wort).

In some embodiments the herbal preparations disclosed herein comprise atleast one herbal extract in the following amount (w/w):

Achillea millefolium from about 0.01% to about 20%;

Aesuculus hippocastanum from about 0.01% to about 20%;

Althaea officinalis from about 0.01% to about 20%;

Avena sativa from about 0.01% to about 25%;

Berberis vulgaris from about 0.01% to about 20%;

Capsella Bursa Pastoris from about 0.01% to about 20%;

Cochlearia officinalis from about 0.01% to about 20%;

Conium maculatium from about 0.01% to about 35%;

Ervum lens from about 0.01% to about 20%;

Hamamelis virginiana from about 0.01% to about 25%;

Hydrastis canadensis from about 0.01% to about 20%;

Matricaria chamomilla from about 0.01% to about 20%;

Nasturtium officinale from about 0.01% to about 15%;

Phytolacca decendra from about 0.01% to about 20%;

Pimpinella saxifraga from about 0.01% to about 20%;

Populas alba from about 0.01% to about 20%;

Populus tremuloides from about 0.01% to about 20%;

Rhus toxicodendron from about 0.01% to about 25%;

Sambucus nigra from about 0.01% to about 20;

Sanguinaria Canadensis from about 0.01% to about 20%;

Scrophularia nodosa from about 0.01% to about 20%;

Smilax medica from about 0.01% to about 20%;

Tussilago farfara from about 0.01% to about 15%;

Veronica officinalis from about 0.010% to about 15%; and

Vincetoxicum officinale from about 0.01% to about 15%.

Throughout the present disclosure the term “about” a certain value meansthat a range of value±20%, and preferably a range of value±10%, iscontemplated. Thus, for example, having about 20% w/w of an ingredientincludes the ingredient being present between 16% and 24%, andpreferably between 18% and 22%.

In some embodiments the herbal preparations disclosed herein compriseAchillea millefolium from about 1% to about 15%; or from about 1% toabout 10%; or from about 1% to about 8%; or from about 1.5% to about 7%;or from about 2% to about 6%. In some embodiments the herbalpreparations disclosed herein comprise Achillea millefolium in about2.5%, while in other embodiments comprise about 5%.

In some embodiments the herbal preparations disclosed herein compriseAesuculus hippocastanum from about 1% to about 15%; or from about 1% toabout 10%; or from about 1% to about 8%; or from about 1.5% to about 7%;or from about 2% to about 6%. In some embodiments the herbalpreparations disclosed herein comprise Aesuculus hippocastanum in about2.4%, while in other embodiments comprise about 5%.

In some embodiments the herbal preparations disclosed herein compriseAlthaea officinalis from about 1% to about 15%; or from about 1% toabout 10%; or from about 1% to about 8%; or from about 1.5% to about 7%;or from about 1.5% to about 5%. In some embodiments the herbalpreparations disclosed herein comprise Althaea officinalis in about2.0%, while in other embodiments comprise about 4%.

In some embodiments the herbal preparations disclosed herein compriseAvena sativa from about 1% to about 25%; or from about 3% to about 20%;or from about 5% to about 17%; or from about 5% to about 15%. In someembodiments the herbal preparations disclosed herein comprise Avenasativa in about 6.8%, while in other embodiments comprise about 14%.

In some embodiments the herbal preparations disclosed herein compriseBerberis vulgaris from about 1% to about 17%; or from about 1% to about15%; or from about 3% to about 12%; or from about 3% to about 10%. Insome embodiments the herbal preparations disclosed herein compriseBerberis vulgaris in about 4.1%, while in other embodiments compriseabout 8%.

In some embodiments the herbal preparations disclosed herein compriseCapsella Bursa Pastoris from about 1% to about 17%; or from about 1% toabout 15%; or from about 1.5% to about 12%; or from about 1.5% to about10%. In some embodiments the herbal preparations disclosed hereincomprise Capsella Bursa Pastoris in about 2.2%, while in otherembodiments comprise about 8%.

In some embodiments the herbal preparations disclosed herein compriseCochlearia officinalis from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 4% to about 10%.In some embodiments the herbal preparations disclosed herein compriseCochlearia officinalis in about 5.1%, while in other embodimentscomprise about 10%.

In some embodiments the herbal preparations disclosed herein compriseConium maculatium from about 1% to about 30%; or from about 1% to about25%; or or from about 3.5% to about 23%. In some embodiments the herbalpreparations disclosed herein comprise Conium maculatium in about 4%, inother embodiments comprise about 12.1%, while in yet other embodimentscomprise about 21%.

In some embodiments the herbal preparations disclosed herein compriseErvum lens from about 1% to about 17%; or from about 1% to about 15%; orfrom about 3% to about 12%; or from about 3% to about 10%. In someembodiments the herbal preparations disclosed herein comprise Ervum lensin about 3.7%, while in other embodiments comprise about 8%.

In some embodiments the herbal preparations disclosed herein compriseHamamelis virginiana from about 1% to about 25%; or from about 3% toabout 20%; or from about 5% to about 17%; or from about 5% to about 15%.In some embodiments the herbal preparations disclosed herein compriseHamamelis virginiana in about 8.9%, while in other embodiments compriseabout 13%.

In some embodiments the herbal preparations disclosed herein compriseHydrastis canadensis from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 3.5% to about10%. In some embodiments the herbal preparations disclosed hereincomprise Hydrastis canadensis in about 5%, in other embodiments compriseabout 6.0%, while in yet other embodiments comprise about 8%.

In some embodiments the herbal preparations disclosed herein compriseMatricaria chamomilla from about 1% to about 17%; or from about 1% toabout 15%; or from about 1.5% to about 12%; or from about 1.5% to about10%. In some embodiments the herbal preparations disclosed hereincomprise Matricaria chamomilla in about 2.2%, while in other embodimentscomprise about 8%.

In some embodiments the herbal preparations disclosed herein compriseNasturtium officinale from about 0.01% to about 12%; or from about 0.01%to about 10%; or from about 0.1% to about 8%; or from about 0.1% toabout 5%. In some embodiments the herbal preparations disclosed hereincomprise Nasturtium officinale in about 0.9%, while in other embodimentscomprise about 2%.

In some embodiments the herbal preparations disclosed herein comprisePhytolacca decendra from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 3.5% to about10%. In some embodiments the herbal preparations disclosed hereincomprise Phytolacca decendra in about 4%, in other embodiments compriseabout 5.8%, while in yet other embodiments comprise about 8%.

In some embodiments the herbal preparations disclosed herein comprisePimpinella saxifraga from about 0.01% to about 12%; or from about 0.01%to about 10%; or from about 0.1% to about 8%; or from about 0.5% toabout 5%. In some embodiments the herbal preparations disclosed hereincomprise Pimpinella saxifraga in about 1.1%, while in other embodimentscomprise about 2%.

In some embodiments the herbal preparations disclosed herein comprisePopulas alba from about 1% to about 17%; or from about 3% to about 15%;or from about 3% to about 12%; or from about 4% to about 10%. In someembodiments the herbal preparations disclosed herein comprise Populasalba in about 4.9%, while in other embodiments comprise about 10%.

In some embodiments the herbal preparations disclosed herein comprisePopulus tremuloides from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 4% to about 10%.In some embodiments the herbal preparations disclosed herein comprisePopulus tremuloides in about 4.8%, while in other embodiments compriseabout 10%.

In some embodiments the herbal preparations disclosed herein compriseRhus toxicodendron from about 1% to about 25%; or from about 3% to about20%; or from about 5% to about 20%; or from about 7% to about 20%. Insome embodiments the herbal preparations disclosed herein comprise Rhustoxicodendron in about 8.3%, while in other embodiments comprise about17%.

In some embodiments the herbal preparations disclosed herein compriseSambucus nigra from about 1% to about 15%; or from about 1% to about10%; or from about 1% to about 8%; or from about 1.5% to about 7%; orfrom about 1.5% to about 6%. In some embodiments the herbal preparationsdisclosed herein comprise Sambucus nigra in about 1.9%, while in otherembodiments comprise about 4%.

In some embodiments the herbal preparations disclosed herein compriseSanguinaria Canadensis from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 4% to about 10%.In some embodiments the herbal preparations disclosed herein compriseSanguinaria Canadensis in about 4.5%, while in other embodimentscomprise about 9%.

In some embodiments the herbal preparations disclosed herein compriseScrophularia nodosa from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 4% to about 10%.In some embodiments the herbal preparations disclosed herein compriseScrophularia nodosa in about 4.0%, while in other embodiments compriseabout 8%.

In some embodiments the herbal preparations disclosed herein compriseSmilax medica from about 1% to about 15%; or from about 1% to about 10%;or from about 1% to about 8%; or from about 1.5% to about 7%; or fromabout 2% to about 6.5%. In some embodiments the herbal preparationsdisclosed herein comprise Smilax medica in about 3.1%, while in otherembodiments, comprise about 6%.

In some embodiments the herbal preparations disclosed herein compriseTussilago farfara from about 0.01% to about 12%; or from about 0.01% toabout 10%; or from about 0.1% to about 8%; or from about 0.1% to about5%. In some embodiments the herbal preparations disclosed hereincomprise Tussilago farfara in about 0.9%, while in other embodimentscomprise about 2%.

In some embodiments the herbal preparations disclosed herein compriseVeronica officinalis from about 0.01% to about 12%; or from about 0.01%to about 10%; or from about 0.1% to about 8%; or from about 0.1% toabout 5%. In some embodiments the herbal preparations disclosed hereincomprise Veronica officinalis in about 0.8%, while in other embodimentscomprise about 2%.

In some embodiments the herbal preparations disclosed herein compriseVincetoxicum officinale from about 0.01% to about 12%; or from about0.01% to about 10%; or from about 0.1% to about 8%; or from about 0.1%to about 5%. In some embodiments the herbal preparations disclosedherein comprise Vincetoxicum officinale in about 0.9%, while in otherembodiments comprise about 2%.

In one embodiment, the herbal preparation disclosed herein comprisesMixture I. Mixture I comprises plant extracts obtained from thefollowing plants: Althaea officinalis; Ervum lens; Populas alba; Populustremuloides; Conium maculatium; Sambucus nigra; Hamamelis virginiana;and Phytolacca decendra.

In another embodiment, the herbal preparation disclosed herein comprisesMixture II. Mixture II comprises plant extracts obtained from thefollowing plants: Conium maculatium; Phytolacca decendra; Pimpinellasaxifraga; Rhus toxicodendron; and Vincetoxicum officinale.

In yet another embodiment, the herbal preparation disclosed hereincomprises Mixture III. Mixture III comprises plant extracts obtainedfrom the following plants: Avena sativa; Aesuculus hippocastanum;Capsella Bursa Pastoris; Hamamelis virginiana; Hydrastis canadensis;Achillea millefolium; and Sanguinaria Canadensis.

In still another embodiment, the herbal preparation disclosed hereincomprises Mixture IV. Mixture IV comprises plant extracts obtained fromthe following plants: Berberis vulgaris; Matricaria chamomilla;Cochlearia officinalis; Hydrastis canadensis; Nasturtium officinale;Scrophularia nodosa; Smilax medica; Tussilago farfara; and Veronicaofficinalis.

In one embodiment, the herbal preparation disclosed herein comprisesMixture V. Mixture V comprises plant extracts obtained from thefollowing plants: Berberis vulgaris; Cochlearia officinalis; Coniummaculatium; Hydrastis canadensis; Matricaria chamomilla; Nasturtiumofficinale; Phytolacca decendra; Pimpinella saxifraga; Rhustoxicodendron; Scrophularia nodosa; Smilax medica; Tussilago farfara;Veronica officinalis; and Vincetoxicum officinale.

In one embodiment, the herbal preparation disclosed herein comprisesMixture VI. Mixture VI comprises plant extracts obtained from thefollowing plants: Achillea millefolium; Aesuculus hippocastanum; Althaeaofficinalis; Avena sativa; Conium maculatium; Ervum lens; Hamamelisvirginiana; Hydrastis canadensis; Phytolacca decendra; Populas alba;Populus tremuloides; Sambucus nigra; and Sanguinaria Canadensis.

In some embodiments, the herbal preparation disclosed herein comprises acombination of Mixture I and Mixture II. In another embodiment, theherbal preparation disclosed herein comprises a combination of Mixture Iand Mixture III. In another embodiment, the herbal preparation disclosedherein comprises a combination of Mixture I and Mixture IV.

In some embodiments, the herbal preparation disclosed herein comprises acombination of Mixture II and Mixture III. In another embodiment, theherbal preparation disclosed herein comprises a combination of MixtureII and Mixture IV.

In some embodiments, the herbal preparation disclosed herein comprises acombination of Mixture III and Mixture IV.

In some embodiments, the herbal preparation disclosed herein comprises acombination of Mixture I, Mixture II and Mixture III. In anotherembodiment, the herbal preparation disclosed herein comprises acombination of Mixture I, Mixture II and Mixture IV. In anotherembodiment, the herbal preparation disclosed herein comprises acombination of Mixture I, Mixture III and Mixture IV. In anotherembodiment, the herbal preparation disclosed herein comprises acombination of Mixture II, Mixture III and Mixture IV.

In another embodiment, the herbal preparation disclosed herein comprisesa combination of Mixture I, Mixture II, Mixture III and Mixture IV.

In some embodiments, the herbal preparation disclosed herein comprises acombination of Mixture V and Mixture VI.

In some embodiments the herbal preparations disclosed herein comprise atleast two herbal extracts each of which is selected from the followinglist and each is present in the following amount (w/w): Achilleamillefolium from about 0.01% to about 20%; Aesuculus hippocastanum fromabout 0.01% to about 20%; Althaea officinalis from about 0.01% to about20%; Avena sativa from about 0.01% to about 25%; Berberis vulgaris fromabout 0.01% to about 20%; Capsella Bursa Pastoris from about 0.01% toabout 20%; Cochlearia officinalis from about 0.01% to about 20%; Coniummaculatium from about 0.01% to about 35%; Ervum lens from about 0.01% toabout 20%; Hamamelis virginiana from about 0.01% to about 25%; Hydrastiscanadensis from about 0.01% to about 20%; Matricaria chamomilla fromabout 0.01% to about 20%; Nasturtium officinale from about 0.01% toabout 15%; Phytolacca decendra from about 0.01% to about 20%; Pimpinellasaxifraga from about 0.01% to about 20%; Populas alba from about 0.01%to about 20%; Populas tremuloides from about 0.01% to about 20%; Rhustoxicodendron from about 0.01% to about 25%; Sambucus nigra from about0.01% to about 20; Sanguinaria Canadensis from about 0.01% to about 20%;Scrophularia nodosa from about 0.01% to about 20%; Smilax medica fromabout 0.01% to about 20%; Tussilago farfara from about 0.01% to about15%; Veronica officinalis from about 0.01% to about 15%; andVincetoxicum officinale from about 0.01% to about 15%.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group I plant extracts and at least oneplant extract from the Group II plant extracts, where the at least oneGroup I plant extract and the at least one Group II plant extract aredifferent.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group I plant extracts and at least oneplant extract from the Group III plant extracts, where the at least oneGroup I plant extract and the at least one Group III plant extract aredifferent.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group I plant extracts and at least oneplant extract from the Group IV plant extracts, where the at least oneGroup I plant extract and the at least one Group IV plant extract aredifferent.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group II plant extracts and at leastone plant extract from the Group III plant extracts, where the at leastone Group II plant extract and the at least one Group III plant extractare different.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group II plant extracts and at leastone plant extract from the Group IV plant extracts, where the at leastone Group II plant extract and the at least one Group IV plant extractare different.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group III plant extracts and at leastone plant extract from the Group IV plant extracts, where the at leastone Group III plant extract and the at least one Group IV plant extractare different.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group I plant extracts, at least oneplant extract from the Group II plant extracts, and at least one plantextract from the Group III plant extracts, where the at least one GroupI plant extract, the at least one Group II plant extract, and the atleast one Group III plant extract are different.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group I plant extracts, at least oneplant extract from the Group II plant extracts, and at least one plantextract from the Group IV plant extracts, where the at least one Group Iplant extract, the at least one Group II plant extract, and the at leastone Group IV plant extract are different.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group I plant extracts, at least oneplant extract from the Group III plant extracts, and at least one plantextract from the Group IV plant extracts, where the at least one Group Iplant extract, the at least one Group III plant extract, and the atleast one Group IV plant extract are different.

In one embodiment, the herbal preparation disclosed herein comprises atleast one plant extract from the Group II plant extracts, at least oneplant extract from the Group III plant extracts, and at least one plantextract from the Group IV plant extracts, where the at least one GroupII plant extract, the at least one Group III plant extract, and the atleast one Group IV plant extract are different.

Group I comprises a plant extract obtained from a plant selected fromthe group consisting of: Althaea officinalis; Ervum lens; Populas alba;Populus tremuloides; Conium maculatium; Sambucus nigra; Hamamelisvirginiana; and Phytolacca decendra.

Group II comprises a plant extract obtained from a plant selected fromthe group consisting of: Conium maculatium; Phytolacca decendra;Pimpinella saxifraga; Rhus toxicodendron; and Vincetoxicum officinale.

Group III comprises a plant extract obtained from a plant selected fromthe group consisting of: Avena sativa; Aesuculus hippocastanum; CapsellaBursa Pastoris; Hamamelis virginiana; Hydrastis canadensis; Achilleamillefolium; and Sanguinaria Canadensis.

Group IV comprises a plant extract obtained from a plant selected fromthe group consisting of: Berberis vulgaris; Matricaria chamomilla;Cochlearia officinalis; Hydrastis canadensis; Nasturtium officinale;Scrophularia nodosa; Smilax medica; Tussilago farfara; and Veronicaofficinalis.

Thus, embodiments of the herbal extracts disclosed herein include themixtures numbered below in Table 1, comprising at least two components,where the components are listed in Table 1.

TABLE 1 No. Component 1 Component 2 1. Achillea millefolium from about0.01% to Aesuculus hippocastanum from about about 20% 0.01% to about 20%2. Achillea millefolium from about 0.01% to Althaea officinalis fromabout 0.01% to about 20% about 20% 3. Achillea millefolium from about0.01% to Avena sativa from about 0.01% to about about 20% 25% 4.Achillea millefolium from about 0.01% to Berberis vulgaris from about0.01% to about 20% about 20% 5. Achillea millefolium from about 0.01% toCochlearia officinalis from about 0.01% to about 20% about 20% 6.Achillea millefolium from about 0.01% to Conium maculatium from about0.01% to about 20% about 35% 7. Achillea millefolium from about 0.01% toErvum lens from about 0.01% to about about 20% 20% 8. Achilleamillefolium from about 0.01% to Hamamelis virginiana from about 0.01%about 20% to about 25% 9. Achillea millefolium from about 0.01% toHydrastis canadensis from about 0.01% to about 20% about 20% 10.Achillea millefolium from about 0.01% to Capsella Bursa Pastoris fromabout 0.01% about 20% to about 20% 11. Achillea millefolium from about0.01% to Matricaria chamomilla from about 0.01% about 20% to about 20%12. Achillea millefolium from about 0.01% to Nasturtium officinale fromabout 0.01% to about 20% about 15% 13. Achillea millefolium from about0.01% to Phytolacca decendra from about 0.01% to about 20% about 20% 14.Achillea millefolium from about 0.01% to Pimpinella saxifraga from about0.01% to about 20% about 20% 15. Achillea millefolium from about 0.01%to Populas alba from about 0.01% to about about 20% 20% 16. Achilleamillefolium from about 0.01% to Populus tremuloides from about 0.01% toabout 20% about 20% 17. Achillea millefolium from about 0.01% to Rhustoxicodendron from about 0.01% to about 20% about 25% 18. Achilleamillefolium from about 0.01% to Sambucus nigra from about 0.01% to about20% about 20% 19. Achillea millefolium from about 0.01% to SanguinariaCanadensis from about 0.01% about 20% to about 20% 20. Achilleamillefolium from about 0.01% to Scrophularia nodosa from about 0.01% toabout 20% about 20% 21. Achillea millefolium from about 0.01% to Smilaxmedica from about 0.01% to about about 20% 20% 22. Achillea millefoliumfrom about 0.01% to Tussilago farfara from about 0.01% to about 20%about 15% 23. Achillea millefolium from about 0.01% to Veronicaofficinalis from about 0.01% to about 20% about 15% 24. Achilleamillefolium from about 0.01% to Vincetoxicum officinale from about 0.01%about 20% to about 15% 25. Aesuculus hippocastanum from about Althaeaofficinalis from about 0.01% to 0.01% to about 20% about 20% 26.Aesuculus hippocastanum from about Avena sativa from about 0.01% toabout 0.01% to about 20% 25% 27. Aesuculus hippocastanum from aboutBerberis vulgaris from about 0.01% to 0.01% to about 20% about 20% 28.Aesuculus hippocastanum from about Cochlearia officinalis from about0.01% to 0.01% to about 20% about 20% 29. Aesuculus hippocastanum fromabout Conium maculatium from about 0.01% to 0.01% to about 20% about 35%30. Aesuculus hippocastanum from about Ervum lens from about 0.01% toabout 0.01% to about 20% 20% 31. Aesuculus hippocastanum from aboutHamamelis virginiana from about 0.01% 0.01% to about 20% to about 25%32. Aesuculus hippocastanum from about Hydrastis canadensis from about0.01% to 0.01% to about 20% about 20% 33. Aesuculus hippocastanum fromabout Capsella Bursa Pastoris from about 0.01% 0.01% to about 20% toabout 20% 34. Aesuculus hippocastanum from about Matricaria chamomillafrom about 0.01% 0.01% to about 20% to about 20% 35. Aesuculushippocastanum from about Nasturtium officinale from about 0.01% to 0.01%to about 20% about 15% 36. Aesuculus hippocastanum from about Phytolaccadecendra from about 0.01% to 0.01% to about 20% about 20% 37. Aesuculushippocastanum from about Pimpinella saxifraga from about 0.01% to 0.01%to about 20% about 20% 38. Aesuculus hippocastanum from about Populasalba from about 0.01% to about 0.01% to about 20% 20% 39. Aesuculushippocastanum from about Populus tremuloides from about 0.01% to 0.01%to about 20% about 20% 40. Aesuculus hippocastanum from about Rhustoxicodendron from about 0.01% to 0.01% to about 20% about 25% 41.Aesuculus hippocastanum from about Sambucus nigra from about 0.01% to0.01% to about 20% about 20% 42. Aesuculus hippocastanum from aboutSanguinaria Canadensis from about 0.01% 0.01% to about 20% to about 20%43. Aesuculus hippocastanum from about Scrophularia nodosa from about0.01% to 0.01% to about 20% about 20% 44. Aesuculus hippocastanum fromabout Smilax medica from about 0.01% to about 0.01% to about 20% 20% 45.Aesuculus hippocastanum from about Tussilago farfara from about 0.01% to0.01% to about 20% about 15% 46. Aesuculus hippocastanum from aboutVeronica officinalis from about 0.01% to 0.01% to about 20% about 15%47. Aesuculus hippocastanum from about Vincetoxicum officinale fromabout 0.01% 0.01% to about 20% to about 15% 48. Althaea officinalis fromabout 0.01% to Avena sativa from about 0.01% to about about 20% 25% 49.Althaea officinalis from about 0.01% to Berberis vulgaris from about0.01% to about 20% about 20% 50. Althaea officinalis from about 0.01% toCochlearia officinalis from about 0.01% to about 20% about 20% 51.Althaea officinalis from about 0.01% to Conium maculatium from about0.01% to about 20% about 35% 52. Althaea officinalis from about 0.01% toErvum lens from about 0.01% to about about 20% 20% 53. Althaeaofficinalis from about 0.01% to Hamamelis virginiana from about 0.01%about 20% to about 25% 54. Althaea officinalis from about 0.01% toHydrastis canadensis from about 0.01% to about 20% about 20% 55. Althaeaofficinalis from about 0.01% to Capsella Bursa Pastoris from about 0.01%about 20% to about 20% 56. Althaea officinalis from about 0.01% toMatricaria chamomilla from about 0.01% about 20% to about 20% 57.Althaea officinalis from about 0.01% to Nasturtium officinale from about0.01% to about 20% about 15% 58. Althaea officinalis from about 0.01% toPhytolacca decendra from about 0.01% to about 20% about 20% 59. Althaeaofficinalis from about 0.01% to Pimpinella saxifraga from about 0.01% toabout 20% about 20% 60. Althaea officinalis from about 0.01% to Populasalba from about 0.01% to about about 20% 20% 61. Althaea officinalisfrom about 0.01% to Populus tremuloides from about 0.01% to about 20%about 20% 62. Althaea officinalis from about 0.01% to Rhus toxicodendronfrom about 0.01% to about 20% about 25% 63. Althaea officinalis fromabout 0.01% to Sambucus nigra from about 0.01% to about 20% about 20%64. Althaea officinalis from about 0.01% to Sanguinaria Canadensis fromabout 0.01% about 20% to about 20% 65. Althaea officinalis from about0.01% to Scrophularia nodosa from about 0.01% to about 20% about 20% 66.Althaea officinalis from about 0.01% to Smilax medica from about 0.01%to about about 20% 20% 67. Althaea officinalis from about 0.01% toTussilago farfara from about 0.01% to about 20% about 15% 68. Althaeaofficinalis from about 0.01% to Veronica officinalis from about 0.01% toabout 20% about 15% 69. Althaea officinalis from about 0.01% toVincetoxicum officinale from about 0.01% about 20% to about 15% 70.Avena sativa from about 0.01% to about Berberis vulgaris from about0.01% to 25% about 20% 71. Avena sativa from about 0.01% to aboutCochlearia officinalis from about 0.01% to 25% about 20% 72. Avenasativa from about 0.01% to about Conium maculatium from about 0.01% to25% about 35% 73. Avena sativa from about 0.01% to about Ervum lens fromabout 0.01% to about 25% 20% 74. Avena sativa from about 0.01% to aboutHamamelis virginiana from about 0.01% 25% to about 25% 75. Avena sativafrom about 0.01% to about Hydrastis canadensis from about 0.01% to 25%about 20% 76. Avena sativa from about 0.01% to about Capsella BursaPastoris from about 0.01% 25% to about 20% 77. Avena sativa from about0.01% to about Matricaria chamomilla from about 0.01% 25% to about 20%78. Avena sativa from about 0.01% to about Nasturtium officinale fromabout 0.01% to 25% about 15% 79. Avena sativa from about 0.01% to aboutPhytolacca decendra from about 0.01% to 25% about 20% 80. Avena sativafrom about 0.01% to about Pimpinella saxifraga from about 0.01% to 25%about 20% 81. Avena sativa from about 0.01% to about Populas alba fromabout 0.01% to about 25% 20% 82. Avena sativa from about 0.01% to aboutPopulus tremuloides from about 0.01% to 25% about 20% 83. Avena sativafrom about 0.01% to about Rhus toxicodendron from about 0.01% to 25%about 25% 84. Avena sativa from about 0.01% to about Sambucus nigra fromabout 0.01% to 25% about 20% 85. Avena sativa from about 0.01% to aboutSanguinaria Canadensis from about 0.01% 25% to about 20% 86. Avenasativa from about 0.01% to about Scrophularia nodosa from about 0.01% to25% about 20% 87. Avena sativa from about 0.01% to about Smilax medicafrom about 0.01% to about 25% 20% 88. Avena sativa from about 0.01% toabout Tussilago farfara from about 0.01% to 25% about 15% 89. Avenasativa from about 0.01% to about Veronica officinalis from about 0.01%to 25% about 15% 90. Avena sativa from about 0.01% to about Vincetoxicumofficinale from about 0.01% 25% to about 15% 91. Berberis vulgaris fromabout 0.01% to Cochlearia officinalis from about 0.01% to about 20%about 20% 92. Berberis vulgaris from about 0.01% to Conium maculatiumfrom about 0.01% to about 20% about 35% 93. Berberis vulgaris from about0.01% to Ervum lens from about 0.01% to about about 20% 20% 94. Berberisvulgaris from about 0.01% to Hamamelis virginiana from about 0.01% about20% to about 25% 95. Berberis vulgaris from about 0.01% to Hydrastiscanadensis from about 0.01% to about 20% about 20% 96. Berberis vulgarisfrom about 0.01% to Capsella Bursa Pastoris from about 0.01% about 20%to about 20% 97. Berberis vulgaris from about 0.01% to Matricariachamomilla from about 0.01% about 20% to about 20% 98. Berberis vulgarisfrom about 0.01% to Nasturtium officinale from about 0.01% to about 20%about 15% 99. Berberis vulgaris from about 0.01% to Phytolacca decendrafrom about 0.01% to about 20% about 20% 100. Berberis vulgaris fromabout 0.01% to Pimpinella saxifraga from about 0.01% to about 20% about20% 101. Berberis vulgaris from about 0.01% to Populas alba from about0.01% to about about 20% 20% 102. Berberis vulgaris from about 0.01% toPopulus tremuloides from about 0.01% to about 20% about 20% 103.Berberis vulgaris from about 0.01% to Rhus toxicodendron from about0.01% to about 20% about 25% 104. Berberis vulgaris from about 0.01% toSambucus nigra from about 0.01% to about 20% about 20% 105. Berberisvulgaris from about 0.01% to Sanguinaria Canadensis from about 0.01%about 20% to about 20% 106. Berberis vulgaris from about 0.01% toScrophularia nodosa from about 0.01% to about 20% about 20% 107.Berberis vulgaris from about 0.01% to Smilax medica from about 0.01% toabout about 20% 20% 108. Berberis vulgaris from about 0.01% to Tussilagofarfara from about 0.01% to about 20% about 15% 109. Berberis vulgarisfrom about 0.01% to Veronica officinalis from about 0.01% to about 20%about 15% 110. Berberis vulgaris from about 0.01% to Vincetoxicumofficinale from about 0.01% about 20% to about 15% 111. Cochleariaofficinalis from about 0.01% to Conium maculatium from about 0.01% toabout 20% about 35% 112. Cochlearia officinalis from about 0.01% toErvum lens from about 0.01% to about about 20% 20% 113. Cochleariaofficinalis from about 0.01% to Hamamelis virginiana from about 0.01%about 20% to about 25% 114. Cochlearia officinalis from about 0.01% toHydrastis canadensis from about 0.01% to about 20% about 20% 115.Cochlearia officinalis from about 0.01% to Capsella Bursa Pastoris fromabout 0.01% about 20% to about 20% 116. Cochlearia officinalis fromabout 0.01% to Matricaria chamomilla from about 0.01% about 20% to about20% 117. Cochlearia officinalis from about 0.01% to Nasturtiumofficinale from about 0.01% to about 20% about 15% 118. Cochleariaofficinalis from about 0.01% to Phytolacca decendra from about 0.01% toabout 20% about 20% 119. Cochlearia officinalis from about 0.01% toPimpinella saxifraga from about 0.01% to about 20% about 20% 120.Cochlearia officinalis from about 0.01% to Populas alba from about 0.01%to about about 20% 20% 121. Cochlearia officinalis from about 0.01% toPopulus tremuloides from about 0.01% to about 20% about 20% 122.Cochlearia officinalis from about 0.01% to Rhus toxicodendron from about0.01% to about 20% about 25% 123. Cochlearia officinalis from about0.01% to Sambucus nigra from about 0.01% to about 20% about 20% 124.Cochlearia officinalis from about 0.01% to Sanguinaria Canadensis fromabout 0.01% about 20% to about 20% 125. Cochlearia officinalis fromabout 0.01% to Scrophularia nodosa from about 0.01% to about 20% about20% 126. Cochlearia officinalis from about 0.01% to Smilax medica fromabout 0.01% to about about 20% 20% 127. Cochlearia officinalis fromabout 0.01% to Tussilago farfara from about 0.01% to about 20% about 15%128. Cochlearia officinalis from about 0.01% to Veronica officinalisfrom about 0.01% to about 20% about 15% 129. Cochlearia officinalis fromabout 0.01% to Vincetoxicum officinale from about 0.01% about 20% toabout 15% 130. Conium maculatium from about 0.01% to Ervum lens fromabout 0.01% to about about 35% 20% 131. Conium maculatium from about0.01% to Hamamelis virginiana from about 0.01% about 35% to about 25%132. Conium maculatium from about 0.01% to Hydrastis canadensis fromabout 0.01% to about 35% about 20% 133. Conium maculatium from about0.01% to Capsella Bursa Pastoris from about 0.01% about 35% to about 20%134. Conium maculatium from about 0.01% to Matricaria chamomilla fromabout 0.01% about 35% to about 20% 135. Conium maculatium from about0.01% to Nasturtium officinale from about 0.01% to about 35% about 15%136. Conium maculatium from about 0.01% to Phytolacca decendra fromabout 0.01% to about 35% about 20% 137. Conium maculatium from about0.01% to Pimpinella saxifraga from about 0.01% to about 35% about 20%138. Conium maculatium from about 0.01% to Populas alba from about 0.01%to about about 35% 20% 139. Conium maculatium from about 0.01% toPopulus tremuloides from about 0.01% to about 35% about 20% 140. Coniummaculatium from about 0.01% to Rhus toxicodendron from about 0.01% toabout 35% about 25% 141. Conium maculatium from about 0.01% to Sambucusnigra from about 0.01% to about 35% about 20% 142. Conium maculatiumfrom about 0.01% to Sanguinaria Canadensis from about 0.01% about 35% toabout 20% 143. Conium maculatium from about 0.01% to Scrophularia nodosafrom about 0.01% to about 35% about 20% 144. Conium maculatium fromabout 0.01% to Smilax medica from about 0.01% to about about 35% 20%145. Conium maculatium from about 0.01% to Tussilago farfara from about0.01% to about 35% about 15% 146. Conium maculatium from about 0.01% toVeronica officinalis from about 0.01% to about 35% about 15% 147. Coniummaculatium from about 0.01% to Vincetoxicum officinale from about 0.01%about 35% to about 15% 148. Ervum lens from about 0.01% to aboutHamamelis virginiana from about 0.01% 20% to about 25% 149. Ervum lensfrom about 0.01% to about Hydrastis canadensis from about 0.01% to 20%about 20% 150. Ervum lens from about 0.01% to about Capsella BursaPastoris from about 0.01% 20% to about 20% 151. Ervum lens from about0.01% to about Matricaria chamomilla from about 0.01% 20% to about 20%152. Ervum lens from about 0.01% to about Nasturtium officinale fromabout 0.01% to 20% about 15% 153. Ervum lens from about 0.01% to aboutPhytolacca decendra from about 0.01% to 20% about 20% 154. Ervum lensfrom about 0.01% to about Pimpinella saxifraga from about 0.01% to 20%about 20% 155. Ervum lens from about 0.01% to about Populas alba fromabout 0.01% to about 20% 20% 156. Ervum lens from about 0.01% to aboutPopulus tremuloides from about 0.01% to 20% about 20% 157. Ervum lensfrom about 0.01% to about Rhus toxicodendron from about 0.01% to 20%about 25% 158. Ervum lens from about 0.01% to about Sambucus nigra fromabout 0.01% to 20% about 20% 159. Ervum lens from about 0.01% to aboutSanguinaria Canadensis from about 0.01% 20% to about 20% 160. Ervum lensfrom about 0.01% to about Scrophularia nodosa from about 0.01% to 20%about 20% 161. Ervum lens from about 0.01% to about Smilax medica fromabout 0.01% to about 20% 20% 162. Ervum lens from about 0.01% to aboutTussilago farfara from about 0.01% to 20% about 15% 163. Ervum lens fromabout 0.01% to about Veronica officinalis from about 0.01% to 20% about15% 164. Ervum lens from about 0.01% to about Vincetoxicum officinalefrom about 0.01% 20% to about 15% 165. Hamamelis virginiana from about0.01% Hydrastis canadensis from about 0.01% to to about 25% about 20%166. Hamamelis virginiana from about 0.01% Capsella Bursa Pastoris fromabout 0.01% to about 25% to about 20% 167. Hamamelis virginiana fromabout 0.01% Matricaria chamomilla from about 0.01% to about 25% to about20% 168. Hamamelis virginiana from about 0.01% Nasturtium officinalefrom about 0.01% to to about 25% about 15% 169. Hamamelis virginianafrom about 0.01% Phytolacca decendra from about 0.01% to to about 25%about 20% 170. Hamamelis virginiana from about 0.01% Pimpinellasaxifraga from about 0.01% to to about 25% about 20% 171. Hamamelisvirginiana from about 0.01% Populas alba from about 0.01% to about toabout 25% 20% 172. Hamamelis virginiana from about 0.01% Populustremuloides from about 0.01% to to about 25% about 20% 173. Hamamelisvirginiana from about 0.01% Rhus toxicodendron from about 0.01% to toabout 25% about 25% 174. Hamamelis virginiana from about 0.01% Sambucusnigra from about 0.01% to to about 25% about 20% 175. Hamamelisvirginiana from about 0.01% Sanguinaria Canadensis from about 0.01% toabout 25% to about 20% 176. Hamamelis virginiana from about 0.01%Scrophularia nodosa from about 0.01% to to about 25% about 20% 177.Hamamelis virginiana from about 0.01% Smilax medica from about 0.01% toabout to about 25% 20% 178. Hamamelis virginiana from about 0.01%Tussilago farfara from about 0.01% to to about 25% about 15% 179.Hamamelis virginiana from about 0.01% Veronica officinalis from about0.01% to to about 25% about 15% 180. Hamamelis virginiana from about0.01% Vincetoxicum officinale from about 0.01% to about 25% to about 15%181. Hydrastis canadensis from about 0.01% to Capsella Bursa Pastorisfrom about 0.01% about 20% to about 20% 182. Hydrastis canadensis fromabout 0.01% to Matricaria chamomilla from about 0.01% about 20% to about20% 183. Hydrastis canadensis from about 0.01% to Nasturtium officinalefrom about 0.01% to about 20% about 15% 184. Hydrastis canadensis fromabout 0.01% to Phytolacca decendra from about 0.01% to about 20% about20% 185. Hydrastis canadensis from about 0.01% to Pimpinella saxifragafrom about 0.01% to about 20% about 20% 186. Hydrastis canadensis fromabout 0.01% to Populas alba from about 0.01% to about about 20% 20% 187.Hydrastis canadensis from about 0.01% to Populus tremuloides from about0.01% to about 20% about 20% 188. Hydrastis canadensis from about 0.01%to Rhus toxicodendron from about 0.01% to about 20% about 25% 189.Hydrastis canadensis from about 0.01% to Sambucus nigra from about 0.01%to about 20% about 20% 190. Hydrastis canadensis from about 0.01% toSanguinaria Canadensis from about 0.01% about 20% to about 20% 191.Hydrastis canadensis from about 0.01% to Scrophularia nodosa from about0.01% to about 20% about 20% 192. Hydrastis canadensis from about 0.01%to Smilax medica from about 0.01% to about about 20% 20% 193. Hydrastiscanadensis from about 0.01% to Tussilago farfara from about 0.01% toabout 20% about 15% 194. Hydrastis canadensis from about 0.01% toVeronica officinalis from about 0.01% to about 20% about 15% 195.Hydrastis canadensis from about 0.01% to Vincetoxicum officinale fromabout 0.01% about 20% to about 15% 196. Capsella Bursa Pastoris fromabout 0.01% Matricaria chamomilla from about 0.01% to about 20% to about20% 197. Capsella Bursa Pastoris from about 0.01% Nasturtium officinalefrom about 0.01% to to about 20% about 15% 198. Capsella Bursa Pastorisfrom about 0.01% Phytolacca decendra from about 0.01% to to about 20%about 20% 199. Capsella Bursa Pastoris from about 0.01% Pimpinellasaxifraga from about 0.01% to to about 20% about 20% 200. Capsella BursaPastoris from about 0.01% Populas alba from about 0.01% to about toabout 20% 20% 201. Capsella Bursa Pastoris from about 0.01% Populustremuloides from about 0.01% to to about 20% about 20% 202. CapsellaBursa Pastoris from about 0.01% Rhus toxicodendron from about 0.01% toto about 20% about 25% 203. Capsella Bursa Pastoris from about 0.01%Sambucus nigra from about 0.01% to to about 20% about 20% 204. CapsellaBursa Pastoris from about 0.01% Sanguinaria Canadensis from about 0.01%to about 20% to about 20% 205. Capsella Bursa Pastoris from about 0.01%Scrophularia nodosa from about 0.01% to to about 20% about 20% 206.Capsella Bursa Pastoris from about 0.01% Smilax medica from about 0.01%to about to about 20% 20% 207. Capsella Bursa Pastoris from about 0.01%Tussilago farfara from about 0.01% to to about 20% about 15% 208.Capsella Bursa Pastoris from about 0.01% Veronica officinalis from about0.01% to to about 20% about 15% 209. Capsella Bursa Pastoris from about0.01% Vincetoxicum officinale from about 0.01% to about 20% to about 15%210. Matricaria chamomilla from about 0.01% Nasturtium officinale fromabout 0.01% to to about 20% about 15% 211. Matricaria chamomilla fromabout 0.01% Phytolacca decendra from about 0.01% to to about 20% about20% 212. Matricaria chamomilla from about 0.01% Pimpinella saxifragafrom about 0.01% to to about 20% about 20% 213. Matricaria chamomillafrom about 0.01% Populas alba from about 0.01% to about to about 20% 20%214. Matricaria chamomilla from about 0.01% Populus tremuloides fromabout 0.01% to to about 20% about 20% 215. Matricaria chamomilla fromabout 0.01% Rhus toxicodendron from about 0.01% to to about 20% about25% 216. Matricaria chamomilla from about 0.01% Sambucus nigra fromabout 0.01% to to about 20% about 20% 217. Matricaria chamomilla fromabout 0.01% Sanguinaria Canadensis from about 0.01% to about 20% toabout 20% 218. Matricaria chamomilla from about 0.01% Scrophularianodosa from about 0.01% to to about 20% about 20% 219. Matricariachamomilla from about 0.01% Smilax medica from about 0.01% to about toabout 20% 20% 220. Matricaria chamomilla from about 0.01% Tussilagofarfara from about 0.01% to to about 20% about 15% 221. Matricariachamomilla from about 0.01% Veronica officinalis from about 0.01% to toabout 20% about 15% 222. Matricaria chamomilla from about 0.01%Vincetoxicum officinale from about 0.01% to about 20% to about 15% 223.Nasturtium officinale from about 0.01% to Phytolacca decendra from about0.01% to about 15% about 20% 224. Nasturtium officinale from about 0.01%to Pimpinella saxifraga from about 0.01% to about 15% about 20% 225.Nasturtium officinale from about 0.01% to Populas alba from about 0.01%to about about 15% 20% 226. Nasturtium officinale from about 0.01% toPopulus tremuloides from about 0.01% to about 15% about 20% 227.Nasturtium officinale from about 0.01% to Rhus toxicodendron from about0.01% to about 15% about 25% 228. Nasturtium officinale from about 0.01%to Sambucus nigra from about 0.01% to about 15% about 20% 229.Nasturtium officinale from about 0.01% to Sanguinaria Canadensis fromabout 0.01% about 15% to about 20% 230. Nasturtium officinale from about0.01% to Scrophularia nodosa from about 0.01% to about 15% about 20%231. Nasturtium officinale from about 0.01% to Smilax medica from about0.01% to about about 15% 20% 232. Nasturtium officinale from about 0.01%to Tussilago farfara from about 0.01% to about 15% about 15% 233.Nasturtium officinale from about 0.01% to Veronica officinalis fromabout 0.01% to about 15% about 15% 234. Nasturtium officinale from about0.01% to Vincetoxicum officinale from about 0.01% about 15% to about 15%235. Phytolacca decendra from about 0.01% to Pimpinella saxifraga fromabout 0.01% to about 20% about 20% 236. Phytolacca decendra from about0.01% to Populas alba from about 0.01% to about about 20% 20% 237.Phytolacca decendra from about 0.01% to Populus tremuloides from about0.01% to about 20% about 20% 238. Phytolacca decendra from about 0.01%to Rhus toxicodendron from about 0.01% to about 20% about 25% 239.Phytolacca decendra from about 0.01% to Sambucus nigra from about 0.01%to about 20% about 20% 240. Phytolacca decendra from about 0.01% toSanguinaria Canadensis from about 0.01% about 20% to about 20% 241.Phytolacca decendra from about 0.01% to Scrophularia nodosa from about0.01% to about 20% about 20% 242. Phytolacca decendra from about 0.01%to Smilax medica from about 0.01% to about about 20% 20% 243. Phytolaccadecendra from about 0.01% to Tussilago farfara from about 0.01% to about20% about 15% 244. Phytolacca decendra from about 0.01% to Veronicaofficinalis from about 0.01% to about 20% about 15% 245. Phytolaccadecendra from about 0.01% to Vincetoxicum officinale from about 0.01%about 20% to about 15% 246. Pimpinella saxifraga from about 0.01% toPopulas alba from about 0.01% to about about 20% 20% 247. Pimpinellasaxifraga from about 0.01% to Populus tremuloides from about 0.01% toabout 20% about 20% 248. Pimpinella saxifraga from about 0.01% to Rhustoxicodendron from about 0.01% to about 20% about 25% 249. Pimpinellasaxifraga from about 0.01% to Sambucus nigra from about 0.01% to about20% about 20% 250. Pimpinella saxifraga from about 0.01% to SanguinariaCanadensis from about 0.01% about 20% to about 20% 251. Pimpinellasaxifraga from about 0.01% to Scrophularia nodosa from about 0.01% toabout 20% about 20% 252. Pimpinella saxifraga from about 0.01% to Smilaxmedica from about 0.01% to about about 20% 20% 253. Pimpinella saxifragafrom about 0.01% to Tussilago farfara from about 0.01% to about 20%about 15% 254. Pimpinella saxifraga from about 0.01% to Veronicaofficinalis from about 0.01% to about 20% about 15% 255. Pimpinellasaxifraga from about 0.01% to Vincetoxicum officinale from about 0.01%about 20% to about 15% 256. Populas alba from about 0.01% to aboutPopulus tremuloides from about 0.01% to 20% about 20% 257. Populas albafrom about 0.01% to about Rhus toxicodendron from about 0.01% to 20%about 25% 258. Populas alba from about 0.01% to about Sambucus nigrafrom about 0.01% to 20% about 20% 259. Populas alba from about 0.01% toabout Sanguinaria Canadensis from about 0.01% 20% to about 20% 260.Populas alba from about 0.01% to about Scrophularia nodosa from about0.01% to 20% about 20% 261. Populas alba from about 0.01% to aboutSmilax medica from about 0.01% to about 20% 20% 262. Populas alba fromabout 0.01% to about Tussilago farfara from about 0.01% to 20% about 15%263. Populas alba from about 0.01% to about Veronica officinalis fromabout 0.01% to 20% about 15% 264. Populas alba from about 0.01% to aboutVincetoxicum officinale from about 0.01% 20% to about 15% 265. Populustremuloides from about 0.01% to Rhus toxicodendron from about 0.01% toabout 20% about 25% 266. Populus tremuloides from about 0.01% toSambucus nigra from about 0.01% to about 20% about 20% 267. Populustremuloides from about 0.01% to Sanguinaria Canadensis from about 0.01%about 20% to about 20% 268. Populus tremuloides from about 0.01% toScrophularia nodosa from about 0.01% to about 20% about 20% 269. Populustremuloides from about 0.01% to Smilax medica from about 0.01% to aboutabout 20% 20% 270. Populus tremuloides from about 0.01% to Tussilagofarfara from about 0.01% to about 20% about 15% 271. Populus tremuloidesfrom about 0.01% to Veronica officinalis from about 0.01% to about 20%about 15% 272. Populus tremuloides from about 0.01% to Vincetoxicumofficinale from about 0.01% about 20% to about 15% 273. Rhustoxicodendron from about 0.01% to Sambucus nigra from about 0.01% toabout 25% about 20% 274. Rhus toxicodendron from about 0.01% toSanguinaria Canadensis from about 0.01% about 25% to about 20% 275. Rhustoxicodendron from about 0.01% to Scrophularia nodosa from about 0.01%to about 25% about 20% 276. Rhus toxicodendron from about 0.01% toSmilax medica from about 0.01% to about about 25% 20% 277. Rhustoxicodendron from about 0.01% to Tussilago farfara from about 0.01% toabout 25% about 15% 278. Rhus toxicodendron from about 0.01% to Veronicaofficinalis from about 0.01% to about 25% about 15% 279. Rhustoxicodendron from about 0.01% to Vincetoxicum officinale from about0.01% about 25% to about 15% 280. Sambucus nigra from about 0.01% toSanguinaria Canadensis from about 0.01% about 20% to about 20% 281.Sambucus nigra from about 0.01% to Scrophularia nodosa from about 0.01%to about 20% about 20% 282. Sambucus nigra from about 0.01% to Smilaxmedica from about 0.01% to about about 20% 20% 283. Sambucus nigra fromabout 0.01% to Tussilago farfara from about 0.01% to about 20% about 15%284. Sambucus nigra from about 0.01% to Veronica officinalis from about0.01% to about 20% about 15% 285. Sambucus nigra from about 0.01% toVincetoxicum officinale from about 0.01% about 20% to about 15% 286.Sanguinaria Canadensis from about 0.01% Scrophularia nodosa from about0.01% to to about 20% about 20% 287. Sanguinaria Canadensis from about0.01% Smilax medica from about 0.01% to about to about 20% 20% 288.Sanguinaria Canadensis from about 0.01% Tussilago farfara from about0.01% to to about 20% about 15% 289. Sanguinaria Canadensis from about0.01% Veronica officinalis from about 0.01% to to about 20% about 15%290. Sanguinaria Canadensis from about 0.01% Vincetoxicum officinalefrom about 0.01% to about 20% to about 15% 291. Scrophularia nodosa fromabout 0.01% to Smilax medica from about 0.01% to about about 20% 20%292. Scrophularia nodosa from about 0.01% to Tussilago farfara fromabout 0.01% to about 20% about 15% 293. Scrophularia nodosa from about0.01% to Veronica officinalis from about 0.01% to about 20% about 15%294. Scrophularia nodosa from about 0.01% to Vincetoxicum officinalefrom about 0.01% about 20% to about 15% 295. Smilax medica from about0.01% to about Tussilago farfara from about 0.01% to 20% about 15% 296.Smilax medica from about 0.01% to about Veronica officinalis from about0.01% to 20% about 15% 297. Smilax medica from about 0.01% to aboutVincetoxicum officinale from about 0.01% 20% to about 15% 298. Tussilagofarfara from about 0.01% to Veronica officinalis from about 0.01% toabout 15% about 15% 299. Tussilago farfara from about 0.01% toVincetoxicum officinale from about 0.01% about 15% to about 15% 300.Veronica officinalis from about 0.01% to Vincetoxicum officinale fromabout 0.01% about 15% to about 15%

In another aspect, disclosed herein are processes for obtaining a plantextract, the process comprising the step of a) mixing the plant withwater and/or another solvent, b) distilling the mixture, and c)collecting the distillate.

In some embodiments, the process further comprises the step of d)separating the aqueous phase from the oil phase and collecting theaqueous phase, after step c).

In some embodiments, the process further comprises the step of e) addingmore of the plant to the aqueous phase and fermenting the mixture, afterstep c) or after step d).

In some embodiments, the process further comprises the step of f)distilling the fermented mixture and collecting the distillate, afterstep e).

In some embodiments, the process further comprises the steps of g)heating the remaining plant material until most of the moisture hasevaporated, after step f), and h) extracting the water soluble salts orhygroscopic salts from the dried plant material. In some embodiments,the remaining plant material is not completely dry. In otherembodiments, the remaining plant material is completely dry. In furtherembodiments, the remaining plant material begins to char. In yet otherembodiments, the remaining plant material begins to incinerate.

In some embodiments, the process further comprises the step of i) addingthe distillate of step e) to the extracted salts of step h).

In another aspect, disclosed herein are herbal extractions obtained bythe above process.

When afflicted with an epidermal condition, the human skin naturallyworks to alleviate the symptoms of the condition. For example, in mostcases, redness, itching, or scaling due to some disorders improve overtime, or until the next episode of a flare up. The herbal preparationsdisclosed herein help the skin in its natural course to reduce theadverse symptoms. Without being bound to a particular theory, thepresent inventors believe that the present herbal preparations providethe skin with the nutrients and building blocks necessary to efficientlyand effectively work to reduce the symptoms.

Thus, in another aspect, disclosed herein are methods of reducingsymptoms associated with a skin condition in a subject, comprisingidentifying the subject in need thereof and administering to the subjectan effective amount of an herbal preparation as disclosed herein.

In some embodiments, the symptoms associated with a skin conditioninclude, but are not limited to, redness, itching, scaling, flaking, dryskin, acne, and the like associated with disorders such as acnevulgaris, psoriasis, eczema, or atopic dermatitis. In certainembodiments, the skin symptom is pruritis (itching), erythema (redness),or excoriations (flaking).

The term “subject” refers to an animal, preferably a mammal, and mostpreferably a human, who is the object of treatment, observation orexperiment. The mammal may be selected from the group consisting ofmice, rats, rabbits, guinea pigs, dogs, cats, sheep, goats, cows,primates, such as monkeys, chimpanzees, and apes, and humans.

The term “effective amount” or “therapeutically effective amount” isused to indicate an amount of an herbal preparation that elicits thebiological response indicated. This response may occur in a tissue,system, animal or human and includes alleviation of the symptoms beingtreated.

In another aspect, disclosed herein are compositions comprising theherbal preparations disclosed herein and at least one physiologicallyacceptable excipient, diluent, or carrier.

The term “excipient” refers to a substance added to the compositionsdisclosed herein. In some cases, the herbal preparations disclosedherein may not by itself be easily administered and/or absorbed by thesubject. In these cases the herbal preparations may be dissolved into ormixed with an excipient. Excipients are also sometimes used to bulk upformulations that contain the herbal preparations, to allow forconvenient and accurate application. In addition to their use in thesingle application quantity, excipients can be used in the manufacturingprocess to aid in the handling of the herbal preparations concerned.Excipients also aid in stabilizing the formulations of the herbalpreparations, for example by keeping the various ingredients in solutionor in suspension, preventing precipitation or crystallization, oradherence to container walls.

The term “carrier” defines a chemical compound that facilitates theincorporation of a compound into cells or tissues. For example dimethylsulfoxide (DMSO) is a commonly utilized carrier as it facilitates theuptake of many organic compounds into the cells or tissues of a subject.

The term “diluent” defines chemical compounds diluted in water that willdissolve the herbal extracts of interest and/or stabilize theformulation of the herbal preparations, including shelf life. Saltsdissolved in buffered solutions are utilized as diluents in the art. Onecommonly used buffered solution is phosphate buffered saline because itmimics the salt conditions of human blood. Since buffer salts cancontrol the pH of a solution at low concentrations, a buffered diluentrarely modifies the benefit of the herbal preparation.

Accordingly, disclosed herein are compositions and methods for thealleviation of the symptoms of skin conditions. The herbal preparationsof the present invention can be delivered or administered to a mammal,(e.g., human subject), alone, or in the form of a formulated compositionwherein the herbal preparation is mixed with suitable carriers orexcipient(s) in an effective amount.

The herbal preparations that are used in the methods disclosed hereincan be administered as formulated compositions comprising the herbalpreparation together with one or more other physiologically acceptablecomponent. Compositions can be in the form of solids (i.e., powders,granules, dragees, tablets, or pills), semi-solids (i.e., gels,slurries, or ointments), or liquids.

Suitable routes of administration may, for example, include oral,topical, rectal, transmucosal, epidural, vaginal, transdermal, or buccaladministration.

Suitable formulations for use in the present invention are found in, forexample, Remington's Pharmaceutical Sciences, Mack Publishing Company,Philadelphia, Pa., 17th ed. (1985) and Langer, Science, 249:1527-1533(1990). The compositions described herein can be manufactured in aconventional manner, e.g., mixing, dissolving, granulating,dragee-making, levigating, emulsifying, encapsulating, entrapping, orlyophilizing processes.

The herbal preparations can be formulated with common excipients,diluents or carriers, and compressed into tablets, or formulated aselixirs or solutions for convenient oral administration. The agents canalso be formulated as sustained release dosage forms and the like.

The compositions disclosed herein may be manufactured in a manner thatis itself known, e.g., by means of conventional mixing, dissolving,granulating, dragee-making, levigating, emulsifying, encapsulating,entrapping or tabletting processes.

Compositions for use in accordance with the present disclosure thus maybe formulated in a conventional manner using one or more physiologicallyacceptable carriers comprising excipients and auxiliaries, whichfacilitate processing of the herbal extracts into herbal preparations.Proper formulation is dependent upon the route of administration chosen.Any of the well-known techniques, carriers, and excipients may be usedas suitable and as understood in the art; e.g., in Remington'sPharmaceutical Sciences, above.

For transmucosal administration, penetrants appropriate to the barrierto be permeated are used in the formulation. Such penetrants aregenerally known in the art.

Compositions suitable for use in accordance with the present inventioninclude compositions wherein the herbal preparations are contained in aneffective amount. The effective amounts for the methods of the presentinvention can depend on a variety of factors, including, e.g., age, bodyweight, general health, sex, diet, time and manner of administration,and the severity of the particular affliction being treated.

EXAMPLES Example 1 Herb Extraction Procedure A:

Herb extraction was achieved by steam distillation. Optionally, one ormore of the steps of oil separation, fermentation, hygroscopic saltextraction, and cohobation was added to the steam distillation step. Theprocedures were as follows.

Steam Distillation

Three liters of deionized water was poured into a 5 L distillationapparatus flask, which was then placed on a sand bath. Herb was added tothe distillation apparatus flask until the flask was about half full. Afilter paper was placed at the joint of the distillation apparatusbefore hooking up the reaction head adaptor. A 2 L receiving flask wasused. Low heat was provided, sufficient for steam to cloud thedistillation apparatus and adapter. After 1.5 L of distillate wascollected, the heat was turned off and the apparatus was allowed tocool. The distillate was removed. One liter of deionized water was addedto the distillation apparatus flask and the distillation was repeated.The distillation was repeated three times.

Oil Separation

The distillate, containing an aqueous phase and an oil phase, wastransferred into a foil drain tube. The stopcock at the end of the draintube was opened and the water was drained off into a 5 L flask.

Fermentation

Herb was placed into the 5 L flask containing the water after oilseparation. The flask was sealed using a secure fermentation lock, andwas incubated at 27° C. for two weeks. Subsequently, the water wasdistilled 5 times and the distillate was saved in a separate container.

Hygroscopic Salt Extraction

The remaining plant material was boiled until the moisture wasevaporated and the plant material began to incinerate. Once theincinerated plant material became grey, it was removed from heat andallowed to cool. A Soxhlet extractor was used to extract the watersoluble salts from the incinerated plant material. The salts wereisolated by rotary evaporation. The extracted salts were placed in acalcining kiln at 600° C. for 1 week. The process was repeated for atotal of 3 times.

Cohobation

The solution obtained after fermentation and the volatile oils wereadded to the isolated salts. The mixture was incubated at 30° C. for 1week. The herbal-medicinal concentrate was separated without disturbingthe sediment. The concentrate can be diluted as needed.

Procedure B:

Each individual plant raw material was subjected to steam distillation.After distillation the leftover material was in the form of wet mass.Additional water was added and the mixture was allowed to ferment in aglass container covered with a cloth lid. Fermentation was continued for7 days at room temperature. During the fermentation the pH wasmonitored. Fermentation was allowed to continue until the mixtures beganto putrefy. After the fermentation was over the biomass was filteredthrough a cloth filter and was subjected to distillation at 80-90° C. toget 30-40% of distillate of filtrate.

The leftover biomass was transferred to trays made from GI/MS andcovered with cloth and was kept for drying in the shade. The drying wascontinued until the biomass became crisp dry, i.e., for about 15-20days. During this time the material was turned around once in a day.After drying the material was subjected to ashing by either 1) burningthe dry mass and collecting the cooled ash, which was then transferredto a crucible and heated further in an oven, or 2) incinerating thebiomass by heating in a crucible at 600° C. The ash obtained isdissolved in distilled water and subjected to further distillation. Alldistillates were combined together and subjected to cohobation, wherethe combined product is heated under reflux for some time.

Example 2 Herbal Preparations

For the experiments detailed below, a unique herbal preparation (HAT-01)was used. Table 2 shows the herbs and their weight percentages withinthis formulation.

TABLE 2 Composition of HAT-01 Percentage Genus Species Common NameComposition Conium maculatum Hemlock 12.1 Hamamelis virginiana Witchhazel 8.9 Rhus toxicodendron Ivy 8.3 Avena sativa Oat 6.8 Hydrastiscanadensis Orange root 6.0 Phytolacca decandra Poke root 5.8 Cochleariaofficinalis Scurvy grass 5.1 Populus alba White Poplar 4.9 Populustremuloides Quaking Aspen 4.8 Sanguinaria canadensis Blood root 4.5Berberis vulgaris Barberry 4.1 Scrophularia nodosa Figwort 4.0 Ervumlens Lentil 3.7 Smilax medica Sarsaparilla 3.1 Achillea millefoliumYarrow 2.5 Aesculus hippocastanum Horsechestnut 2.4 Capsella BursaPastoris Shepherd's Purse 2.3 Matricaria chamomilla Chamomile 2.2Althaea officinalis Mallow 2.0 Sambucus nigra Elderberry 1.9 Pimpinellasaxifraga Burnet 1.1 Vincetoxicum officinale Swallow wort 0.9 Nasturtiumofficinale Watercress 0.9 Tussilago farfara Colts foot 0.9 Veronicaofficinalis Speedwell 0.8 Total 100

Furthermore, to compare constituent efficacy and synergism, HAT-01 wasalso partially formulated into two: HAT-01:P1 and HAT-01:P2 as describedin Tables 3 and 4, respectively. These herbs have established clinicalbenefit, and are considered safe for clinical use in chronicinflammatory conditions.

TABLE 3 Composition of HAT-01: P1 Percentage Genus Species CompositionConium maculatum 21 Rhus toxicodendron 17 Cochlearia officinalis 10Hydrastis canadensis 8 Phytolacca decandra 8 Berberis vulgaris 8Scrophularia nodosa 8 Smilax medica 6 Matricaria chamomilla 4 Pimpinellasaxifraga 2 Vincetoxicum officinale 2 Nasturtium officinale 2 Tussilagofarfara 2 Veronica officinalis 2 Total 100

TABLE 4 Composition of HAT-01: P2 Percentage Genus Species CompositionHamamelis virginiana 13 Avena sativa 14 Populus alba 10 Populustremuloides 10 Sanguinaria canadensis 9 Ervum lens 8 Achilleamillefolium 5 Aesculus hippocastanum 5 Hydrastis canadensis 5 CapsellaBursa Pastoris 5 Althaea officinalis 4 Conium maculatum 4 Phytolaccadecandra 4 Sambucus nigra 4 Total 100

Our NMR analyses of the ingredients in HAT-01 have confirmed therelative concentrations of components, and absolute concentrations ofknown substances. Of note, results from ¹H-NMR spectroscopic analyses ofHAT-01 showed no evidence of a corticosteroid moiety, which correlateswell with our findings that no changes were observed in serum cortisollevels in mice before and after treatment with 10% oral HAT-01, anddemonstrating that HAT-01 effects are nonsteroidal.

Example 3 Benefits of HAT-01 in Patients with Psoriasis: Pilot Trial

To assess the benefits of HAT-01 in psoriasis, we performed an 8-week,open-label, two armed study (HAT-01 and OTC medication arm) in patientswith mild to moderate chronic plaque psoriasis. Patients (aged 18 to 70years) with stable chronic plaque psoriasis of at least 6 monthsduration with a psoriasis body surface area (BSA)≦10% were included. Allareas with the exception of the face, groin and axillae were treated.Patients with current or recent malignancies, severe asthma, infections,uncontrolled hypertension, and/or those treated with systemic or topicalcorticosteroid or immunosuppressant agents were excluded from the study.Patients with abnormal screening laboratory values, as well as pregnantwomen, were also excluded from the study. Patients were not allowed touse any medicated cosmetics that might influence the outcome of thestudy. A total of 16 patients fulfilling psoriasis inclusion criteriawere enrolled into an exploratory 8 week, open-label study designed toinvestigate the safety, utility and tolerability of HAT-01. Patientswere enrolled into one of two arms: (a) twice-daily application ofHAT-01 (n=9 patients) or (b) twice-daily application of over-the-countertopical medications which are first-line therapy for patients withpsoriasis and included topical vitamin D₃ analog calcipotriene ortopical retinoids (n=7 patients). Approximately 300 μl of HAT-01 wasapplied per lesion, prepared as a 10% dilution of the concentratedherbal extracts in 4.9% EtOH. The primary outcome was defined as thepercentage change from baseline in the body surface area affected bypsoriasis at weeks 2, 4, and 8 following treatment. Safety evaluationsincluded tolerability assessments and incidence of adverse events.

Patients were evaluated for changes in total body surface area,erythema, scaling, and plaque resolution. Patients with moderate diseaseactivity who received HAT-01 demonstrated an average 42% reduction inthe percentage in body surface area affected by psoriasis at 8 weeks,whereas those treated with a control OTC topical vitamin D₃ analogcalcipotriene and topical retinoids exhibited a reduction in thepercentage in body surface area affected by psoriasis by only 12% (FIG.1). Significant resolution in erythema and scaling with changes inplaque elevation (from that of marked to slight) was observed in 8 of 9patients after 8 weeks of HAT-01 treatment.

HAT-01 was well tolerated, with no treatment-related adverse eventsobserved throughout the 8-week trial. At week 8, all patients treatedwith HAT-01 had no reports of skin atrophy, pruritus, orburning/stinging. In contrast at 8 weeks of treatment, 4 of 7 patientsthat were treated with control OTC topical vitamin D₃ analogcalcipotriene exhibited local treatment-site irritation, burningsensation, and pain.

Example 4 Therapeutic Effects of HAT-01 in Patients with Acne Vulgaris:Clinical Vignettes

To assess the effects of HAT-01 in acne vulgaris, an open-label study ofHAT-01 in subjects with mild to moderate (grade I and II) acne vulgariswas undertaken at an outpatient setting of a private practice clinic.Subjects aged 18 to 50 years of age with ≧three inflammatory ornon-inflammatory lesions of papules or pustules in the face wereincluded. Exclusion criteria included: severe acne, the use of anyanti-acne medications within the preceding four weeks, or subjects withcystic lesions or any acne requiring systemic treatment. Subjects werenot allowed to use any medicated cosmetics that might influence theoutcome of the study. A total of 4 patients fulfilling criteria wereenrolled. The primary efficacy outcome was defined as the change frombaseline of the total lesion count. Subjects were asked to follow a 4week regimen of twice daily applications of HAT-01 (300 μl applied perlesion, prepared as a 10% dilution of the concentrated herbal extractsin 4.9% EtOH). An analysis of the post-treatment inflammatory andnon-inflammatory lesion counts demonstrated a highly significantreduction of scores from baseline to 4 week time points, indicative ofthe therapeutic potential of HAT-01 in acne vulgaris. HAT-01 was welltolerated, with no treatment-related adverse events observed throughoutthe 4-week trial including no reports of skin atrophy, pruritus, orburning/stinging at the local treatment-site.

Example 5 Clinical Studies

Methodology

The clinical trial was conducted in a contract research organizationsetting with three investigators (dermatologists) in a multi-centersite. Patients were block randomized from a central location into eachstudy arm. Patients were assessed both before and throughout the courseof treatment at each visit using by SCORAD and a Patient Benefit Index(which assesses AD patient-relevant treatment benefit). SCORAD values,ranging from 0 to 103, are classified as mild (<15), moderate (16-40)and severe (>41), and are calculated as(0.2×Area)+(3.5×Erythema+Edema+Crust+Excoriation+Lichenification+Dryness)+(pruritis+sleeploss). All three investigators were given prior training and testing forstandardized scoring of SCORAD in AD, an approach that has been found tobe significantly beneficial for minimizing observer variability.

Our primary objective was the efficacy of HAT-01, HAT-01P1, and/orHAT-01P2 in the reduction of pruritus in atopic dermatitis patients.

Our secondary objective(s) were to

(a) evaluate the therapeutic benefit of HAT-01, HAT-01P1, and/orHAT-01P2 in atopic dermatitis as measured by the SCORAD (SCORing AtopicDermatitis),

(b) evaluate the therapeutic benefit of HAT-01, HAT-01P1, and/orHAT-01P2 to reduce pruritus from patient's perspective as assessed bythe Patient Benefit Index, and

(c) safety and tolerability of HAT-01, HAT-01P1, and/or HAT-01P2 inatopic dermatitis patients.

Double Blinded Randomization: A double blind approach where bothinvestigators and patients are blinded was used. Investigators performedenrollment and blinded assignment using blinded labels. Assignments wererotated through enrollment by investigators to enable random continuousenrollment and avoid selection bias.

Treatment: Atopic dermatitis patients fulfilling eligibility (inclusionand exclusion criteria) were provided with an informed consent. Atopical formulation of HAT-01, HAT-01P1, and/or HAT-01P2 was randomlyand blindly provided (without patient knowledge) and followed through 2,4, 8, and 12 weeks after treatment. Patients were assessed both beforeand throughout the course of treatment (each visit) for the followingindices: SCORAD (SCORing Atopic Dermatitis), Patient Benefit Index. Eachpatient also had up to 10 mls of blood drawn prior to (0) and at 4, and12, weeks post-therapy to distinguish laboratorial and cytokine changesover time. Serum from 64 patients with AD on an approved randomizedsingle blind placebo-controlled clinical trial of HAT-01, placebo andpartial formulations of HAT-01 were obtained for all groups at 3 timepoints (0, 4, 12 weeks).

Therapeutic Effects of HAT-01 in Patients with Atopic Dermatitis: PilotTrial

To correlate our findings in human patients with AD, we performed anexploratory 10-week, open-label study to evaluate the utility of HAT-01in atopic dermatitis. Significant resolution of symptoms and signs of ADwas observed through a Three Item Severity score in 15 of 18 patientsafter 4 weeks of topical HAT-01 treatment, with no relapses at 10-weeksof follow up. We then performed pilot clinical studies to evaluate theutility of HAT-01 in atopic dermatitis. Patients with severe asthmaand/or those treated with systemic or topical (greater than mediumstrength) corticosteroids or immunosuppressant agents were excluded fromthe study. An exploratory 10-week, open-label study was designed toinvestigate the safety, efficacy and tolerability of a twice-dailyapplication of a topical formulation of HAT-01 in AD. A total of 18patients fulfilling diagnostic criteria for AD were enrolled and placedon a regimen of twice daily application of a topical formulation ofHAT-01 (300 μl of 1:10). FIG. 2 portrays the design outline of thispilot trial. The primary efficacy outcome was defined as the change inthe Three Item Severity score (TIS score) of AD based on the evaluationof erythema, oedema/papulation and excoriation in each representativelesion. Significant resolution of symptoms and signs of AD was observedin 83% of patients (15 of 18) after 4 weeks of HAT-01 treatment, with norelapses at 8-week or 10-week follow up (FIG. 3). Patients with severedisease activity pretreatment (TIS score>6) demonstrated an average54.6% reduction in disease activity at 4-weeks, and an average of 77.1%reduction in disease activity by 10-weeks (FIG. 3). Of note, asignificant reduction in edema and erythema was observed within 2-weeks,which was followed by improvements in oozing and excoriations within 4weeks following treatment with HAT-01. Significant improvement inxerosis (dryness) was also immediately observed, while improvement inlichenification (thickening) took up to 10 weeks for effectiveresolution.

AD: Therapeutic effects of HAT-01 in patients with atopic dermatitis:Randomized placebo-controlled trial. To further investigate the safety,efficacy and tolerability of a twice-daily application of a topicalformulation of HAT-01 in atopic dermatitis (AD), a total of 64 patientsfulfilling inclusion criteria for AD were enrolled into a randomizedplacebo-controlled single (patient) blind clinical trial with a regimenof twice daily application of a topical formulation of HAT-01 (300 μl of1:10). The primary efficacy outcome was defined as the change in theSeverity Scoring of Atopic Dermatitis (SCORAD) values. SCORAD values,ranging from 0 to 103, are classified as mild (<15), moderate (16-40)and severe (>41), and are calculated as(0.2×Area)+(3.5×Erythema+Edema+Crust+Excoriation+Lichenification+Dryness)+(pruritis+sleeploss). As shown in FIG. 4, significant resolution of symptoms and signsof AD was observed in 84% of patients after 4 weeks of HAT-01 treatment,with sustained effects and no relapses at 8-week or 12-weeks of followup (FIG. 4). Placebo (vehicle) treatment had no significant effect onSCORAD values, and treatment with partial formulations HAT-01:P1 andHAT-01:P2 had only minimal effects relative to treatment with wholeHAT-01 (FIG. 4). Significant reduction in edema and erythema wasobserved within 4-weeks, which was followed by improvements in oozingand excoriations within 8 weeks following treatment with HAT-01.Significant improvement in xerosis was also observed at 4 weeks, whileimprovement in lichenification took up to 12 weeks for effectiveresolution. Importantly, HAT-01 was well tolerated and notreatment-related adverse events were observed throughout the 12-weekpilot trial, indicating the safe and potent therapeutic benefit ofHAT-01 in a majority of the patients studied with AD.

What is claimed is:
 1. A composition comprising a mixture of plantextracts, wherein the mixture comprises: a) at least one Group I plantextract and at least one Group II plant extract, wherein the at leastone Group I plant extract and the at least one Group II plant extractare different; b) at least one Group I plant extract and at least oneGroup III plant extract, wherein the at least one Group I plant extractand the at least one Group III plant extract are different; c) at leastone Group I plant extract and at least one Group IV plant extracts,wherein the at least one Group I plant extract and the at least oneGroup IV plant extract are different; d) at least one Group II plantextract and at least one Group III plant extracts, wherein the at leastone Group II plant extract and the at least one Group III plant extractare different; e) at least one Group II plant extract and at least oneGroup IV plant extract, wherein the at least one Group II plant extractand the at least one Group IV plant extract are different; f) at leastone Group III plant extract and at least one Group IV plant extract,wherein the at least one Group III plant extract and the at least oneGroup IV plant extract are different; g) at least one Group I plantextract, at least one Group II plant extract, and at least one Group IIIplant extract, wherein the at least one Group I plant extract, the atleast one Group II plant extract, and the at least one Group III plantextract are different; h) at least one Group I plant extract, at leastone Group II plant extract, and at least one Group IV plant extract,wherein the at least one Group I plant extract, the at least one GroupII plant extract, and the at least one Group IV plant extract aredifferent; i) at least one Group I plant extract, at least one Group IIIplant extract, and at least one Group IV plant extract, wherein the atleast one Group I plant extract, the at least one Group III plantextract, and the at least one Group IV plant extract are different; orj) at least one Group II plant extract, at least one Group III plantextract, and at least one Group IV plant extracts, wherein the at leastone Group II plant extract, the at least one Group III plant extract,and the at least one Group IV plant extract are different; wherein:Group I comprises a plant extract obtained from a plant selected fromthe group consisting of: Althaea officinalis; Ervum lens; Populas alba;Populus tremuloides; Conium maculatium; Sambucus nigra; Hamamelisvirginiana; and Phytolacca decendra; Group II comprises a plant extractobtained from a plant selected from the group consisting of: Coniummaculatium; Phytolacca decendra; Pimpinella saxifraga; Rhustoxicodendron; and Vincetoxicum officinale; Group III comprises a plantextract obtained from a plant selected from the group consisting of:Avena sativa; Aesuculus hippocastanum; Capsella Bursa Pastoris;Hamamelis virginiana; Hydrastis canadensis; Achillea millefolium; andSanguinaria Canadensis; and Group IV comprises a plant extract obtainedfrom a plant selected from the group consisting of: Berberis vulgaris;Matricaria chamomilla; Cochlearia officinalis; Hydrastis canadensis;Nasturtium officinale; Scrophularia nodosa; Smilax medica; Tussilagofarfara; and Veronica officinalis.
 2. The composition of claim 1,wherein the composition comprises at least two herbal extracts each ofwhich is present in the following amount (w/w): Achillea millefoliumfrom about 0.01% to about 20%; Aesuculus hippocastanum from about 0.01%to about 20%; Althaea officinalis from about 0.01% to about 20%; Avenasativa from about 0.01% to about 25%; Berberis vulgaris from about 0.01%to about 20%; Capsella Bursa Pastoris from about 0.01% to about 20%;Cochlearia officinalis from about 0.01% to about 20%; Conium maculatiumfrom about 0.01% to about 35%; Ervum lens from about 0.01% to about 20%;Hamamelis virginiana from about 0.01% to about 25%; Hydrastis canadensisfrom about 0.01% to about 20%; Matricaria chamomilla from about 0.01% toabout 20%; Nasturtium officinale from about 0.01% to about 15%;Phytolacca decendra from about 0.01% to about 20%; Pimpinella saxifragafrom about 0.01% to about 20%; Populas alba from about 0.01% to about20%; Populus tremuloides from about 0.01% to about 20%; Rhustoxicodendron from about 0.01% to about 25%; Sambucus nigra from about0.01% to about 20; Sanguinaria Canadensis from about 0.01% to about 20%;Scrophularia nodosa from about 0.01% to about 20%; Smilax medica fromabout 0.01% to about 20%; Tussilago farfara from about 0.01% to about15%; Veronica officinalis from about 0.01% to about 15%; andVincetoxicum officinale from about 0.01% to about 15%.
 4. Thecomposition of claim 1, comprising an extract selected from the groupconsisting of: i) Althaea officinalis from about 1% to about 15%; orfrom about 1% to about 10%; or from about 1% to about 8%; or from about1.5% to about 7%; or from about 1.5% to about 5%; ii) Ervum lens fromabout 1% to about 17%; or from about 1% to about 15%; or from about 3%to about 12%; or from about 3% to about 10%; iii) Populas alba fromabout 1% to about 17%; or from about 3% to about 15%; or from about 3%to about 12%; or from about 4% to about 10%; iv) Populus tremuloidesfrom about 1% to about 17%; or from about 3% to about 15%; or from about3% to about 12%; or from about 4% to about 10%; v) Conium maculatiumfrom about 1% to about 30%; or from about 1% to about 25%; or from about3.5% to about 23%; vi) Sambucus nigra from about 1% to about 15%; orfrom about 1% to about 10%; or from about 1% to about 8%; or from about1.5% to about 7%; or from about 1.5% to about 6%; vii) Hamamelisvirginiana from about 1% to about 25%; or from about 3% to about 20%; orfrom about 5% to about 17%; or from about 5% to about 15%; and viii)Phytolacca decendra from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 3.5% to about10%.
 5. The composition of claim 1, comprising an extract selected fromthe group consisting of: i) Conium maculatium from about 1% to about30%; or from about 1% to about 25%; or from about 3.5% to about 23%; ii)Phytolacca decendra from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 3.5% to about10%; iii) Pimpinella saxifraga from about 0% to about 12%; or from about0% to about 10%; or from about 0.1% to about 8%; or from about 0.5% toabout 5%; iv) Rhus toxicodendron from about 1% to about 25%; or fromabout 3% to about 20%; or from about 5% to about 20%; or from about 7%to about 20%; and v) Vincetoxicum officinale from about 0% to about 12%;or from about 0% to about 10%; or from about 0.1% to about 8%; or fromabout 0.1% to about 5%.
 6. The composition of claim 1, comprising anextract selected from the group consisting of: i) Avena sativa fromabout 1% to about 25%; or from about 3% to about 20%; or from about 5%to about 17%; or from about 5% to about 15%; ii) Aesuculus hippocastanumfrom about 1% to about 15%; or from about 1% to about 10%; or from about1% to about 8%; or from about 1.5% to about 7%; or from about 2% toabout 6%; iii) Capsella Bursa Pastoris from about 1% to about 17%; orfrom about 1% to about 15%; or from about 1.5% to about 12%; or fromabout 1.5% to about 10%; iv) Hamamelis virginiana from about 1% to about25%; or from about 3% to about 20%; or from about 5% to about 17%; orfrom about 5% to about 15%; v) Hydrastis canadensis from about 1% toabout 17%; or from about 3% to about 15%; or from about 3% to about 12%;or from about 3.5% to about 10%; vi) Achillea millefolium from about 1%to about 15%; or from about 1% to about 10%; or from about 1% to about8%; or from about 1.5% to about 7%; or from about 2% to about 6%; andvii) Sanguinaria Canadensis from about 1% to about 17%; or from about 3%to about 15%; or from about 3% to about 12%; or from about 4% to about10.
 7. The composition of claim 1, comprising an extract selected fromthe group consisting of: i) Berberis vulgaris from about 1% to about17%; or from about 1% to about 15%; or from about 3% to about 12%; orfrom about 3% to about 10%; ii) Matricaria chamomilla from about 1% toabout 17%; or from about 1% to about 15%; or from about 1.5% to about12%; or from about 1.5% to about 10%; iii) Cochlearia officinalis fromabout 1% to about 17%; or from about 3% to about 15%; or from about 3%to about 12%; or from about 4% to about 10%; iv) Hydrastis canadensisfrom about 1% to about 17%; or from about 3% to about 15%; or from about3% to about 12%; or from about 3.5% to about 10%; v) Nasturtiumofficinale from about 0% to about 12%; or from about 0% to about 10%; orfrom about 0.1% to about 8%; or from about 0.1% to about 5%; vi)Scrophularia nodosa from about 1% to about 17%; or from about 3% toabout 15%; or from about 3% to about 12%; or from about 4% to about 10%;vii) Smilax medica from about 1% to about 15%; or from about 1% to about10%; or from about 1% to about 8%; or from about 1.5% to about 7%; orfrom about 2% to about 6.5%; viii) Tussilago farfara from about 0% toabout 12%; or from about 0% to about 10%; or from about 0.1% to about8%; or from about 0.1% to about 5%; and ix) Veronica officinalis fromabout 0% to about 12%; or from about 0% to about 10%; or from about 0.1%to about 8%; or from about 0.1% to about 5%.
 8. The composition of claim1, further comprising a physiologically acceptable carrier, diluent, orexcipient.
 9. The composition of claim 1, wherein the composition isformulated for topical application.
 10. The composition of claim 1,wherein the composition is an aqueous solution.
 11. A method of reducingsymptoms associated with a skin condition in a subject, comprisingidentifying the subject in need thereof and administering to the subjectan effective amount of the composition of claim
 1. 12. The method ofclaim 11, wherein the skin condition is associated with acne vulgaris,psoriasis, eczema, or atopic dermatitis.
 13. The method of claim 11,wherein the skin condition is pruritis, erythema, or excoriations.